Esters of Mono‐ and Alkenyl Carboxylic Acids and Mono‐ and Polyalcohols

Abstract

This volume contains three chapters reviewing 12 classes of organic compounds called esters. This chapter (Chapter 57) reviews esters of monocarboxylic acids and mono- and polyalcohols and esters of alkenyl carboxylic acids and monoalcohols; Chapter 58 reviews esters of aromatic monocarboxylic acids and monoalcohols, esters of monocarboxylic acids and di-, tri-, and polyalcohols, dicarboxylic acid esters, alkenyl dicarboxylic esters, esters of aromatic diacids, and tricarboxylic acid esters; and Chapter 59 covers esters of carbonic acid and orthocarbonic acid, esters of organic phosphorous compounds, esters of monocarboxylic halogenated acids, alkanols, or haloalcohols, and organic silicon esters. The sequence of the compounds has been organized according to the chemical structure of the major functional metabolites. This involves the ester hydrolyzates, primarily the acid and secondarily the alcohol. The reason for this sequence was the general observation that the degree of toxic effect, in addition to that of the original material, more often was the result of the toxicity of the acid rather than the response of the alcohol. Esters are important from an industrial hygiene perspective since exposure can occur during the process of manufacturing esters, the process of manufacturing materials containing or composed of esters, handling and use of products containing or composed of esters, and treatment of wastes containing esters. In turn, exposure to esters is important from a toxicological perspective because of the correlated observations of adverse physiological responses exhibited by laboratory animals and humans. Overviews of the physical, chemical, and toxicological (i.e., physiological responses) properties of many subclasses of esters and/or of specific compounds are provided. In addition, summaries of relative manufacturing and use information are included for many compounds. Chemically, esters are organic compounds commonly formed via the combination of an acid, typically an organic (COOH) mono- or polyacid, and a hydroxyl (OH) group of a mono- or polyalcohol or phenol; water (HOH) is generated as a by-product of the reaction. The esters are widely used in industry and commerce. They can be prepared by the reactions of acids with alcohols by reacting metal salts of acids with alkyl halides, acid halides with alcohols, or acid anhydrides with alcohols by the interchange of radicals between esters. Most esters exist in liquid form at ambient temperatures, but some possess lower boiling points than their original starting materials. They are relatively water insoluble, except for the lower molecular weight members. Their flash points are in the flammable range. The monocarboxylic acid esters have high volatility and pleasant odors, whereas the di- and polyacid esters are relatively nonvolatile and exhibit essentially no odor. The monocarboxylic esters occur frequently in natural products, as, for example, in fruits, to which they lend their pleasant odor and taste. Because of the different properties of esters from the original acids and alcohols, esterification can be used for their isolation or for chemically protecting specific carboxy or hydroxy functions. Absorbed esters and/or metabolites derived from biotransformed esters can initiate toxic effects in some mammalian systems, including humans, and cause adverse physiological responses. Indeed, the underlying causes of physiological responses are due to initial interactions biochemically within a system. Within these chapters, a summary of reviewed literature will reveal that, in general, toxic effects associated with exposure to various esters include primary irritation to ocular, upper and lower respiratory, and dermal systems; depression of the central nervous system (CNS) (e.g., anesthesia and narcosis); dermal hypersensitization; impact to the gastrointestinal, hepatic, and renal systems; abnormal cardiac rhythm; and carcinogenesis. Indeed, these and some additional effects are based predominantly on rodent studies. A review of the literature reported here, however, indicates that the most commonly reported effects in animals and humans are irritation and, to some extent, CNS depression. Data are reported in this chapter for several classes of esters, including formates, acetates, acrylates and methacrylates, propionates, and lactates. Most of the aliphatic esters possess some degree of irritation on exposed surfaces. Practically all the common aliphatic and aromatic esters, except for some phosphates used as plasticizers, are inert. At the most, minor degrees of irritation may follow inhalation of heated vapors or prolonged skin exposure. Some of the literature also suggests that reported skin sensitization appears more likely in the presence of impurities or side products. Many of the materials are so inert that any LD50 value is impractical to determine. Specific pathology is usually absent even when the materials are fed in massive quantities to the point of nutritional deprivation. Oily or watery excretion products, sometimes observed at high feeding levels, indicate lack of absorption. The apparent nontoxicity may also be a sign of rapid hydrolysis, metabolism, and excretion. The resins are completely inert, unabsorbed in the gastrointestinal tract, and nonirritant at the surface of the skin and pulmonary system. Keywords: acetates; acetoacetals; acrylates; alkyl carboxylic acids; butyrates; formates; inhalation; lactates; methacrylates; propionates; sugarcane